Effect of Glucosamine Sulfate on Hip Osteoarthritis

“…GS is the most frequently used form of glucosamine for the treatment of osteoarthritis (Reginster et al 2001;Pavelka et al 2002) but its efficiency in the treatment of osteoarthritis is still controversial (Vlad et al 2007;Rozendaal et al 2008;Felson 2008). Most often, its suggested mechanism of action is considered to involve its effect on GAG synthesis, although inhibition of interleukin-1-mediated catabolism by GS has also been proposed (Gouze et al 2002;Largo et al 2003;Neil et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension

Pöytäkangas

Jauhiainen

et al. 2009

Cell Tissue Res

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Low oxygen tension may change the dependence of chondrocytes on exogenous carbohydrate sources. In this study, we have investigated whether glucosamine sulphate (GS) stimulates proteoglycan synthesis, the mRNA expression of aggrecan and of type II collagen, and UDP-sugar levels in bovine primary chondrocytes under a low oxygen (O(2)) atmosphere. Chondrocytes from bovine femoral condyles were cultivated with or without GS or sulphate at various concentrations in low- (5.5 mM) or high-glucose (25 mM) DMEM under either a 5% or 20% O(2) atmosphere for 2 or 8 days after isolation. The mRNA expression of aggrecan and type II collagen and the synthesis of glycosaminoglycan (GAG) were determined by quantitative real-time reverse transcription with polymerase chain reaction and a [(35)S]-sulphate incorporation assay, respectively. Aggrecan promoter activity was analysed by a dual-luciferase reporter gene assay. Intracellular UDP-N-acetylhexosamines (UDP-HexN), UDP-glucuronic acid and UDP-hexoses were analysed by reversed-phase high-performance liquid chromatography electrospray ionization mass spectrometry. A low (5%) O(2) atmosphere significantly increased GAG synthesis, mRNA expression of aggrecan and of type II collagen and aggrecan promoter activity in bovine primary chondrocytes. A high (1 mM) concentration of GS was required to increase the level of UDP-HexN. However, GS did not increase GAG synthesis, aggrecan promoter activity or mRNA expression of aggrecan and of type II collagen. Interestingly, a 5% O(2) atmosphere increased the level of UDP-HexN in 8-day cultures without GS treatment. Thus, exogenous GS does not change chondrocyte metabolism, whereas a 5% O(2) atmosphere stimulates extracellular matrix production in bovine primary chondrocytes. The balance of UDP-sugars is changed under a 5% O(2) atmosphere for longer culture periods.

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“…Interestingly, at certain stage, investigators should have known that such a dosage regimen was going to yield concentration substantially lower than those used in in vitro or in animal studies (13,27,52). Also, the positive trend toward GlcN's beneficial effect reported by several authors (8,37,46,51) should have alarmed them of the possibility of under-dosing. Nevertheless, to the best of our knowledge, no attempt was made to test a higher dosage regimen even by the investigators involved in the GAIT study who used a pharmaceutical grade formulation.…”

Section: Dose-effect Relationship and Bioequivalencementioning

confidence: 99%

“…It is important to note that the results of some of the GlcN clinical trials with negative outcomes do not totally rule out potential benefits or trend toward efficacy of the treatment in some patients (8,37,46,51). This, coupled with the possibility of under-dosing with the less than claimed 1500 mg/day regimens, highlight the need for clinical trials using higher pharmaceutical grade GlcN doses or formulations that yield greater plasma concentrations.…”

Section: Inconsistency Of Commercial Products and Its Consequence On mentioning

confidence: 99%

The Glucosamine Controversy; A Pharmacokinetic Issue

Aghazadeh‐Habashi

Jamali

2011

J Pharm Pharm Sci

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Glucosamine (GlcN) is a naturally occurring aminosugar that is widely used to treat osteoarthritis despite controversial clinical trial results. Animal studies, on the other hand, unequivocally suggest anti-inflammatory and disease modifying effects for GlcN. Many explanations have been offered as to the root of the controversy. They include superiority of a crystalline sulphate salt over HCl, industry bias, insensitive assessment metrics and poor methodology. Herein, we rule out a difference in bioequivalence between GlcN salts and that of chemically equivalent doses and suggest additional factors; i.e., inconsistency in the chemical potency of some products used, under-dosing of patients as well as variable and erratic bioavailability indices for the lack of GlcN efficacy observed in some studies. Clinical trials using higher doses of pharmaceutical grade GlcN or formulations with greater bioavailability should yield positive results. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Effect of Glucosamine Sulfate on Hip Osteoarthritis

Abstract: Glucosamine sulfate was no better than placebo in reducing symptoms and progression of hip osteoarthritis. International Standard Randomised Controlled Trial Number: ISRCTN54513166.

Cited by 118 publications

References 28 publications

Effect of Glucosamine on Pain-Related Disability in Patients With Chronic Low Back Pain and Degenerative Lumbar Osteoarthritis

Effect of Glucosamine on Pain-Related Disability in Patients With Chronic Low Back Pain and Degenerative Lumbar Osteoarthritis

Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension

The Glucosamine Controversy; A Pharmacokinetic Issue

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